Quercetin
Quercetin
Generic Name
Quercetin
Mechanism
Quercetin is a dietary flavonoid whose pharmacologic actions arise from multiple, inter‑related mechanisms:
• Antioxidant activity – scavenges reactive oxygen species (ROS) and up‑regulates endogenous antioxidant enzymes (SOD, catalase, glutathione peroxidase).
• Anti‑inflammatory signaling – inhibits key transcription factors such as NF‑κB and AP‑1, reducing expression of pro‑inflammatory cytokines (TNF‑α, IL‑6, IL‑1β).
• Mitochondrial protection – preserves mitochondrial membrane potential and reduces cytochrome c release.
• Ion channel modulation – blocks L‑type calcium channels and K⁺ channels in vascular smooth muscle, leading to vasodilatory effects.
• Anti‑viral activity – interferes with viral replication by inhibiting viral polymerases and proteases in models of influenza, HIV, and SARS‑CoV‑2.
• Modulation of signal‑transduction pathways – down‑regulates PI3K/Akt and MAPK pathways implicated in cancer cell proliferation.
These actions underpin quercetin’s use in *anti‑inflammatory*, *antioxidant*, *cardioprotective*, *neuroprotective*, and *oncolytic* strategies.
Pharmacokinetics
- Absorption: Oral bioavailability is low (~1–2 %) due to poor solubility; absorption is enhanced by co‑administration with phospholipids or by forming nanoparticles.
- Distribution: Widely distributed; high protein binding (~70 %). Concentrations accumulate in the liver, kidneys, lungs, and adipose tissue.
- Metabolism: Primarily glucuronidated and sulfated in the intestinal mucosa and liver by UGT and SULT enzymes.
- Elimination: Excreted mainly via feces (≈70 %) and urine (≈20 %). Half‑life ranges 4–7 h after a single dose; steady state ~3–4 days.
- Drug interactions: Inhibits CYP3A4, CYP1A2, and P‑gp at high concentrations; may potentiate or diminish activity of drugs metabolized by these pathways.
Indications
| Indication | Rationale | Typical Dose (Supplementary) |
| Chronic inflammation (arthralgia, osteoarthritis) | Anti‑NF‑κB and antioxidant effects | 500–1000 mg/day orally |
| Allergic rhinitis | H1‑receptor stabilization & mast‑cell degranulation inhibition | 500–800 mg/day |
| Cardiovascular protection (hypertension, atherosclerosis) | L‑type Ca²⁺ channel blockade, endothelial NO production | 150–300 mg/day |
| Neuroprotection (PD, AD models) | Mitigates oxidative brain injury | 400–600 mg/day |
| Antiviral adjunct (influenza, HSV, SARS‑CoV‑2) | Inhibits viral polymerases in vitro | 500–1000 mg/day |
| Exercise performance | Attenuates muscle oxidative stress | 200–400 mg/day prior to activity |
> *Note*: Many indications derive from in‑vitro or animal studies; human clinical trials are limited and dose ranges are primarily based on supplement use.
Contraindications
- Pregnancy & Lactation – data sparse; avoid if possible.
- Severe hepatic impairment – metabolism is hepatic; impaired clearance may occur.
- Peptic ulcer disease – high oral doses can irritate GI mucosa; use with caution.
- Hemorrhagic disorders – quercetin can inhibit platelet aggregation; caution in patients on anticoagulants (warfarin) or aspirin.
- Drug interactions – may potentiate CYP3A4 inhibitors/inducers and P‑gp modulators.
Dosing
- Form: Capsule, tablet, or liquid extract (standardized to ≥15 % quercetin).
- Oral: 500–1000 mg/day in divided doses (morning + evening) to improve tolerance.
- With food: Food, especially fats, increases absorption—take with a meal.
- Duration: Short‑term (≤4 weeks) for acute inflammation; long‑term (>6 months) for chronic conditions is generally tolerated but requires periodic safety checks.
Adverse Effects
| System | Adverse Effect | Notes |
| GI | Nausea, abdominal discomfort, diarrhea, mild epigastric pain | Rare at therapeutic doses |
| Musculoskeletal | Headache, myalgia | Transient |
| Hematologic | Rare allergic reactions, hemolysis in G6PD deficiency | Screen if at risk |
| Hepatic | Mild transaminase elevation (≤3× ULN) | Monitor LFTs |
| Anticoagulant | Slight INR increase when co‑administered with warfarin | Check INR frequently |
Serious: Allergic reaction (urticaria, anaphylaxis) is extremely uncommon; withdraw if signs appear.
Monitoring
- Baseline and periodic:
- Liver function tests (ALT, AST, ALP, bilirubin) every 4–6 weeks in chronic users.
- Kidney function (serum creatinine, eGFR) if renal disease suspected.
- INR/bleeding profile if on anticoagulants.
- Symptoms: Monitor for GI upset, skin rash, jaundice.
Clinical Pearls
- Boost your bioavailability: Pair quercetin with phospholipid complexes or take with tartaric acid to form a more soluble quercetin–tartarate salt.
- Avoid concurrent high‑dose NSAIDs: Both can inhibit COX‑2, increasing GI irritation risk.
- Watch the dosing schedule: Splitting into double‑daily doses reduces peak‑dose GI upset and sustains antioxidant levels.
- Consider nano‑formulations: Several clinical studies show >10‑fold higher plasma concentrations with *solid lipid nanoparticles*, especially useful when a rapid onset is desired.
- Screen G6PD patients: Quercetin’s radical scavenging might worsen hemolysis in G6PD deficiency.
- Beware in anticoagulated patients: Even though quercetin is mild, it can add to platelet inhibition—monitor for bleeding signs.
- Use a reputable source: Supplements vary in content and purity; choose products certified by USP, NSF, or Informed‑Choice.
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• *This drug card is intended for educational purposes and should not replace individualized clinical judgment.*